首页 >>2014年09期
基因多态性对儿童肥胖和代谢异常的影响
作者:张美仙 赵小元 席波 沈玥 吴丽君 程红 侯冬青 米杰

摘要:

目的在中国儿童中验证肥胖相关基因多态性对肥胖及代谢异常的影响。方法研究对象来源于2004年北京儿童青少年代谢综合征研究(BCAMS)的3 503618岁学龄儿童,包括肥胖组1 229名、超重组655名和正常体重组1 619名。采用盐析法从外周血白细胞中提取DNA。使用ABI PrismsTM~7900实时荧光定量PCR仪对11个基因的多态性位点(FTO rs9939609MC4R rs17782313GNPDA2 rs10938397FAIM2 rs7138803BDNF rs6265NPC1 rs1805081PCSK1 rs6235KCTD15 rs29941BAT2 rs2844479SEC16B rs10913469SH2B1 rs4788102)进行分型检测。采用中国肥胖问题工作组推荐的BMI分类标准判定超重和肥胖。采用多因素分析基因多态性对儿童期肥胖相关性状的影响。采用错误发现率(FDR)方法校正多重检验。结果控制年龄、性别和青春发育期的影响后,FTO rs9939609~AMC4R rs17782313~CGNPDA2 rs10938397~GFAIM2 rs7138803~A等位基因增加儿童BMI(β=0.3520.747)、体脂百分比(β= 0.5681.113)、腰围(β=0.8851.649)和腰围身高比(β=0.0050.010)的水平(P0.01),BDNF rs6265~G等位基因增加儿童BMI(β=0.251P=0.020)和体脂百分比(β=0.416P=0.040)水平。校正多重检验后,除rs6265与体脂百分比的关联消失外,其余SNP与肥胖评价指标的关联仍有意义。FTO rs9939609~AMC4R rs17782313~CGNPDA2 rs10938397~GFAIM2 rs7138803~ABDNF rs6265~G等位基因增加儿童肥胖风险(OR=1.38695%CI1.1711.642OR=1.36795%CI1.1961.563OR=1.24295%CI1.1021.400OR=1.15495%CI1.0211.305OR=1.15695%CI1.0311.296);其中FAIM2 rs7138803仅增加男童肥胖风险(OR=1.23495%CI1.0431.460)。校正多重检验后,上述SNP与儿童肥胖的关联仍有意义。同时,GNPDA2 rs10938397~G等位基因还增加儿童胰岛素抵抗风险(OR=1.205,95%CI1.0691.359),但在控制BMI后关联消失。结论FTO rs9939609~AMC4R rs17782313~CGNPDA2 rs10938397~GFAIM2 rs7138803~A增加儿童肥胖评价指标(BMI、体脂百分比、腰围和腰围身高比)的水平及肥胖风险,BDNF rs6265~G等位基因增加儿童BMI水平和肥胖风险;其中GNPDA2 rs10938397~G通过影响BMI可增加儿童胰岛素抵抗的风险。

关键词:儿童;肥胖症;基因多态性;代谢异常

Abstract:

ObjectiveTo examine the impact of single nucleotide polymorphisms  in obesity~related genes on risk of obesity and metabolic disorder in childhood.MethodsA total of 3 503 Chinese children aged 6 to 18 years participated in the study, including 1 229 obese, 655 overweight and 1 619 normal weight children (diagnosed by the Chinese age~ and sex~ specific BMI cutoffs).Body size parameters were assessed and venipuncture blood samples were collected after a 12~hour overnight fast.Plasma glucose, insulin and serum lipid profiles were measured.Genomic DNA was isolated from peripheral blood white cells using the salt fractionation method.A total of 11 single nucleotide polymorphisms were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system(Applied Biosystems, Foster City, CA, USA)(FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, FAIM2 rs7138803, BDNF rs6265, NPC1 rs1805081, PCSK1 rs6235, KCTD15 rs29941, BAT2 rs2844479, SEC16B rs10913469 and SH2B1 rs4788102).Multiple factor analysis was performed to estimate the association between the variant and obesity~related traits.The false discovery rate (FDR) approach was used to correct for multiple comparisons.ResultsAfter sex, age and pubertal stage adjustment and correction for multiple testing, the rs9939609~A,rs17782313~C,rs10938397~G, and rs7138803~A alleles were associated with higher BMI(β=0.352~0.747), fat mass percentage(β=0.568~1.113),waist circumference(β=0.885~1.649) and waist~to~height ratio(β=0.005~0.010)(all P values0.01) in Chinese children. The rs6265~G allele increased BMI(β=0.251,P=0.020).The rs9939609~A, rs17782313~C, and rs10938397~G and rs6265~G alleles were also associated with risk of obesity (OR=1.386,95%CI:1.171~1.642;OR=1.367,95%CI:1.196~1.563;OR=1.242,95%CI:1.102~1.400;OR=1.156,95%CI:1.031~1.296).Rs7138803 was associated with risk of obesity only in boys(OR=1.234,95%CI:1.043~1.460). GNPDA2 rs10938397~G allele was associated with risk of insulin resistance(OR=1.205,95%CI:1.069~1.359), but there was no significance after adjusting for BMI.ConclusionThe association of FTO rs9939609~A, MC4R rs17782313~C, GNPDA2 rs10938397~G, and FAIM2 rs7138803~A with higher BMI, fat mass percentage, waist circumference, and waist~to height ratio and risk of obesity, and BDNF rs6265~G allele may increase BMI and obesity risk in Chinese children.GNPDA2 rs10938397~G may increase the risk of childhood insulin resistance depending on BMI.

Key words: Child;Obesity;Gene polymorphism;Metabolic disorder

发表日期:2014/9

引用本文:

图/表:

    暂无图表

参考文献:

[1]马军,蔡赐河,王海俊,等. 1985—2010年中国学生超重与肥胖流行趋势[J]. 中华预防医学杂志,2012,46(9):776780.
[2]Herman KM, Craig CL, Gauvin L, et al. Tracking of obesity and physical activity from childhood to adulthood: The physical activity longitudinal study[J]. Int J Pediatr Obes,2009,4(4):281288.
[3]Allison DB, Kaprio J, Korkeila M, et al. The heritability of body mass index among an international sample of monozygotic twins reared apart[J]. Int J Obes Relat Metab Disord,1996,20(6):501506.
[4]Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity[J]. Behav Genet,1997,27(4):325351.
[5]Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity[J]. Science, 2007,316(5826):889894.
[6]Loos RJ, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity[J]. Nat Genet,2008,40(6):768775.
[7]Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index[J]. Nat Genet,2010,42(11):937948.
[8]Thorleifsson G, Walters GB, Gudbjartsson DF, et al. Genomewide association yields new sequence variants at seven loci that associate with measures of obesity[J]. Nat Genet,2009,41(1):1824.
[9]米杰,程红,侯冬青,等. 北京市2004年2~18岁儿童青少年超重和肥胖流行现状[J]. 中华流行病学杂志,2006,27(6):469474.
[10]Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee[J]. World Health Organ Tech Rep Ser, 1995,854:1452.
[11]季成叶, 中国肥胖问题工作组. 中国学龄儿童青少年超重、肥胖筛查体重指数值分类标准[J]. 中华流行病学杂志,2004,25(2):97102.
[12]Kuczmarski RJ, Ogden CL, GrummerStrawn LM, et al. CDC growth chart: United States[J]. Adv Data, 2000,314:127.
[13]米杰, 王天有, 孟玲慧, 等. 中国儿童青少年血压参照标准的研究制定[J]. 中国循证儿科杂志, 2010,5(1):414.
[14]American Diabetes Association. Diagnosis and classification of diabetes mellitus[J]. Diabetes Care, 2013, 36 Suppl 1:S6774.
[15]《中华儿科杂志》编辑委员会,中华医学会儿科学分会儿童保健学组,中华医学会儿科学分会心血管学组,等.儿童青少年血脂异常防治专家共识[J]. 中华儿科学杂志,2009,47(6):426428.
[16]Cornelis MC, Qi L, Zhang C, et al. Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry[J]. Ann Intern Med,2009,150(8):541550.
[17]Fava C, Sjgren M, Montagnana M, et al. Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes[J]. Hypertension,2013,61(2):319326.
[18]席波,张美仙,沈玥,等. 体脂和肥胖相关基因多态性与生活行为因素交互作用对学龄儿童肥胖的影响[J]. 中华流行病学杂志,2010,31(7): 737741.
[19]Wang J, Thornton JC, Russell M, et al. Asians have lower body mass index (BMI) but higher percent body fat than do whites: comparisons of anthropometric measurements[J]. Am J Clin Nutr,1994,60(1):2328.
[20]He W, Zhang S, Song A, et al. Greater abdominal fat accumulation is associated with higher metabolic risk in Chinese than in white people: an ethnicity study[J]. PLoS One,2013,8(3):e58688.
[21]Wang J, Mei H, Chen W, et al. Study of eight GWASidentified common variants for association with obesityrelated indices in Chinese children at puberty[J]. Int J Obes(Lond),2012,36(4):542547.
[22]Cecil JE, Tavendale R, Watt P, et al. An obesityassociated FTO gene variant and increased energy intake in children[J]. N Engl J Med,2008,359(24):25582566.
[23]Whlén K, Sjlin E, Hoffstedt J. The common rs9939609 gene variant of the fat mass and obesityassociated gene FTO is related to fat cell lipolysis[J]. J Lipid Res, 2008,49(3):607611.
[24]Russell MA, Morgan NG. Conditional expression of the FTO gene product in rat INS1 cells reveals its rapid turnover and a role in the profile of glucoseinduced insulin secretion[J]. Clin Sci(Lond),2011,120(9):403413.
[25]Guo J, Ren W, Li A, et al. Fat mass and obesityassociated gene enhances oxidative stress and lipogenesis in nonalcoholic fatty liver disease[J]. Dig Dis Sci, 2013,58(4):10041009.
[26]Olza J, Ruperez AI, GilCampos M, et al. Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a casecontrol multicentre study[J]. BMC Med Genet,2013,14:123.
[27]曹凌峰,罗飞宏,支涤静,等. FTO基因SNP rs9939609, rs1421085多态性与儿童青少年肥胖及其代谢指标的相关性研究[J]. 中国循证儿科杂志,2010,5(1):4650.

用户评论 0条

用户名: 密码: 登陆 注册
 
  • 9
  • 3
  •  4 : 页次:0/0页 共0条记录 5条/每页
    关于我们 | 专家风采 | 会员注册 | 继续教育
    地 址:北京市西城区东河沿街69号正弘大厦511室 邮 编:100052
    电话:010-51322302
    版权所有 中华医学会及中华预防医学杂志编辑部
    京ICP备 07035254 号